Evidence map›Paper›PMID 39680178›Full record

ArticleJournal of neurology2024

Antibodies against SARS-CoV-2 spike protein in the cerebrospinal fluid of COVID-19 patients and vaccinated controls: a multicentre study.

Vardan Nersesjan, Marion Ingeborg Boldingh, Else Quist Paulsen, Maria Argren, Einar Høgestøl, Anne Hege Aamodt, Trine Haug Popperud, Daniel Kondziella, Charlotte Sværke Jørgensen, Veronika Vorobieva Solholm Jensen and 1 more

Abstract readMulticenter Study
PubMed Publisher
In one paragraph

Article in Journal of neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Vardan NersesjanCopenhagen Research Center for Biological and Precision Psychiatry, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark. vardan.nersesjan@regionh.dk.ORCID http://orcid.org/0000-0001-7786-9626
Marion Ingeborg BoldinghDepartment of Neurology, Oslo University Hospital, Oslo, Norway.
Else Quist PaulsenDepartment of Microbiology, Oslo University Hospital, Oslo, Norway.
Maria ArgrenDepartment of Neurology, Oslo University Hospital, Oslo, Norway.
Einar HøgestølDepartment of Neurology, Oslo University Hospital, Oslo, Norway.
Anne Hege AamodtDepartment of Neurology, Oslo University Hospital, Oslo, Norway.
Trine Haug PopperudDepartment of Neurology, Oslo University Hospital, Oslo, Norway.
Daniel KondziellaDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Charlotte Sværke JørgensenDepartment of Virus and Microbiological Special Diagnostics, Statens Serum Institut, Copenhagen, Denmark.
Veronika Vorobieva Solholm JensenDepartment of Virus and Microbiological Special Diagnostics, Statens Serum Institut, Copenhagen, Denmark.
Michael E BenrosCopenhagen Research Center for Biological and Precision Psychiatry, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark.

Funding

Lundbeck Foundation R349-2020-658
6 · The paper itself

Abstract

introductionSARS-CoV-2 antibodies in the cerebrospinal fluid (CSF) of COVID-19 patients possibly reflect blood-cerebrospinal fluid barrier (BCB) disruption due to systemic inflammation. However, some studies indicate that CSF antibodies signal a neurotropic infection. Currently, larger studies are needed to clarify this, and it is unknown if CSF antibodies appear solely after infection or also after COVID-19 vaccination. Therefore, we aimed to investigate the CSF dynamics of SARS-CoV-2 antibodies in a multicenter study of COVID-19 patients and vaccinated controls.

methodsA cohort study of Danish and Norwegian COVID-19 patients and controls investigated with a lumbar puncture (April 2020-December 2022). Serum and CSF were analysed locally for routine investigations, and centrally at Statens Serum Institut (Danish governmental public health institute) for SARS-CoV-2 IgG antibodies against the spike protein using the Euroimmun (quantitative) and Wantai (qualitative) assays. Primary outcome was the quantity of CSF SARS-CoV-2 antibodies post-COVID versus post-vaccination. Secondary outcomes included regression models examining the relationship between CSF antibodies and serum levels, albumin ratio, CSF pleocytosis, COVID-19 severity, and temporal antibody dynamics.

resultsWe included 124 individuals (Mean [SD] age 47.2 [16.6]; 59.7% males surviving COVID-19 and controls. Of these, 86 had paired CSF-serum testing. Antibody-index calculations did not support a SARS-CoV-2 brain infection. Multi-variate regression revealed that CSF SARS-CoV-2 antibodies were most strongly influenced by serum antibody levels and BCB permeability, as measured by increasing albumin ratio. CSF antibody levels displayed a dose-response relationship (p < 0.0001) influenced by preceding vaccinations or infections. CSF antibody levels (median [IQR]) were highest among those both previously infected and vaccinated, 100.0 [25.0-174.0], and those vaccinated without prior infection, 85.0 [12.0-142.0], and lowest among previously infected individuals without preceding vaccination, 5.9 [2.7-55.1], (p = 0.003). SARS-CoV-2 antibodies in CSF were also detected via qualitative assays in the COVID-19 (46.8%) and vaccinated (78.6%) groups, p = 0.03.

conclusionSARS-CoV-2 antibodies detected in CSF can be derived following both infection and vaccination for COVID-19. CSF antibody levels increase in a dose-response relationship with the number of prior infections and vaccinations and are most strongly influenced by serum antibody levels and BCB permeability. These findings stress the importance of carefully interpreting CSF antibody results when assessing neurological complications following infections not categorized as neurotropic.

Indexed as

Antibodies, ViralCOVID-19COVID-19 VaccinesSARS-CoV-2Spike Glycoprotein, CoronavirusAdultAgedCohort StudiesDenmarkFemaleHumansImmunoglobulin GMaleMiddle AgedNorwayVaccinationAntibodies, ViralCOVID-19 VaccinesImmunoglobulin GSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2Blood–brain-barrierCOVID-19CSFEncephalitisVaccination

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.